Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia

E. G. Nabel, L. Shum, V. J. Pompili, Z. Y. Yang, H. San, Bing Shu Hong Bing Shu, S. Liptay, L. Gold, D. Gordon, R. Derynck, G. J. Nabel

Research output: Contribution to journalArticlepeer-review

343 Scopus citations


The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor β1 (TGF-β1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-β1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-β1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-β1 into porcine arteries. Expression of TGF-β1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-β1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-β1 was greater, and cellular proliferation was less prominent. These findings show that TGF-β1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.

Original languageEnglish (US)
Pages (from-to)10759-10763
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - 1993
Externally publishedYes


  • cellular proliferation
  • extracellular matrix
  • gene expression
  • gene transfer

ASJC Scopus subject areas

  • General


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